Exposure to ionizing radiation increases the risk of developing cancer at low doses and is used to control cancer at high doses.
Ionizing radiation can elicit an 'activated' phenotype in some cells that promotes rapid and persistent remodelling of the extracellular matrix, through the induction of proteases and growth factors, as well as chronic production of reactive oxygen species.
The rapid and dynamic cell biology that occurs in irradiated tissues indicates the existence of a microenvironment-mediated damage-response programme. Some mechanisms of the ionizing radiation-induced microenvironment include chronic inflammation and persistent production of transforming growth factor-β.
These cellular and tissue responses to ionizing radiation can have non-targetted effects on non-irradiated cells, such as induction of genomic instability and neoplastic progression.
The functional consequences of exposing an organism to ionizing radiation are a product of DNA damage, cell loss and altered tissue microenvironments that promote carcinogenesis and might affect responses to anticancer therapies.
Radiation rapidly and persistently alters the soluble and insoluble components of the tissue microenvironment. This affects the cell phenotype, tissue composition and the physical interactions and signalling between cells. These alterations in the microenvironment can contribute to carcinogenesis and alter the tissue response to anticancer therapy. Examples of these responses and their implications are discussed with a view to therapeutic intervention.
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Thanks to Noelle F. Metting for assistance with preparing Box 1.
The authors declare no competing financial interests.
- IONIZING RADIATION
Energy from isotopic decay or produced by electromagnetic excitation that is capable of producing ionizations, directly or indirectly, while traversing matter.
- CYTOKINES, GROWTH FACTORS AND CHEMOKINES
Proteins that convey information between cells, through secretion and interaction with receptors. Signalling by these molecules regulates cell proliferation, differentiation, motility, adhesion and apoptosis.
Organ compartment that performs the function of a tissue — for example, tissue-specific epithelium.
Organ compartment serving as the connective tissue framework; includes fibroblasts, immune defense cells and fat cells.
- EXTRACELLULAR MATRIX
(ECM). An insoluble protein scaffold on which cells reside. The ECM provides the structure and attachment sites, and signals through cell surface receptors. Epithelial cells, endothelial cells and adipocytes rest on a specialized ECM called the basement membrane. Interstitial ECM is collagen-rich.
- REACTIVE OXYGEN SPECIES
Highly reactive chemical radicals generated as products of oxygen degradation.
- DIRECT EFFECTS
Interaction of energy with matter, resulting in ionization.
- INDIRECT EFFECTS
Interaction of energy with water, resulting in production of reactive oxygen species.
Sparsely ionizing radiation that has similar effects to γ-rays, and is used in radiotherapy. X-rays result from electron energy-transitions with the atom or through the deceleration of high kinetic-energy electrons.
Sparsely ionizing radiation that has similar effects to X-rays, and is used in radiotherapy. γ-Radiation results from excited and unstable nuclei of radioactive materials.
- STEM-CELL NICHE
The restricted, specialized microenvironment that mediates stem-cell expansion and differentiation.
Blood vessels outlined with cuffs of neutrophils.
Biological factors that increase markers of DNA damage such as mutation frequency, chromosome aberrations or sister chromatid exchange.
Short range, high linear-energy transfer radiation from isotopic decay that gives rise to clusters of ionized molecules.
- TISSUE REMODELLING
Activation process of extracellular matrix (ECM) degradation and production that affects the turnover and composition of ECM proteins. This process accompanies wound healing, inflammation and large scale apoptotic events, such as mammary gland involution. It can be induced by ionizing radiation, either subclinically or at a pathological level, preceding fibrosis.
When donor and recipient tissues share the same major histocompatibilty complex antigens.
Genetically identical — for example, fully inbred mouse strains.
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Barcellos-Hoff, M., Park, C. & Wright, E. Radiation and the microenvironment – tumorigenesis and therapy. Nat Rev Cancer 5, 867–875 (2005). https://doi.org/10.1038/nrc1735
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